Abstract We propose to design and test a lightweight iridium-electrode nitric oxide generator that provides medical grade NO gas from air and electricity, to serve as an economical, portable, battery-driven source of NO for ambulatory and home inhalation therapy. These features will make it feasible to conduct robust outpatient trials leading to a novel selective pulmonary vasodilator therapy for chronic lung disease and heart failure. Inhaled NO produces pulmonary vasodilation without systemic vasodilation, which is a significant issue with other currently available therapies. In December 1999, the US Food and Drug Administration (FDA), approved inhaled NO for the treatment of hypoxic term or near-term infants with hypoxic respiratory failure (HRF) since which time inhaled NO has been a life-saving intervention for hospitalized infants to treat acute pulmonary hypertension. However tank-delivered NO is not practical for portable applications due to its weight and complexity of delivery. Our technology will enable inhaled NO as a portable therapy for these debilitating chronic diseases. Our collaborators in the Zapol lab at MGH recently reported on data obtained from testing a 110V AC-powered bedside NO generating device in a lamb model of pulmonary artery hypertension (PAH). This prototype was subsequently tested in a human proof of concept (POC) trial in 6 healthy volunteers and to date 5 patients with PAH in the MGH catheterization lab. Third Pole and the Zapol lab have commenced work under NHLBI B-BIC/NCAI grant #U54HL119145 to optimize the electrode design of an NO generator for use with mechanical ventilators and anesthesia machines. We will gather user requirements, test and develop a battery-powered portable iridium electrode inhaled NO generator with optimal materials and design to enable trials of safe long-term ambulatory inhalation therapy with NO.